Quantitative measurements of small molecules are essential to pharmaceutical sciences research. Discovery of the mechanisms of disease pathogenesis for development of new therapeutic strategies requires the assessment of post-translational modifications of peptides and nucleic acids and quantitative measurements of small molecules in complex biological matrices. The most specific and sensitive method of quantification of these targets is through triple quadrupole mass spectrometry. There are currently no triple quadrupole mass spectrometers available for use by the fourteen PHS-funded University of Pittsburgh investigators listed as the user group in this proposal. In fact, there are only four such systems at the University, of which only one is less that seven years old and all are very heavily utilized and thus not available to meet the needs of our group. The lack of such instrumentation is a particular problem for investigators conducting clinical studies due to the large number of samples that accompanies such work. The specific aim of this proposal is to request funds from the National Center for Research Resources to acquire a Dionex UltiMate 3000 HPLC with an API 4000 QTRAP hybrid triple quadrupole/linear ion trap mass spectrometer to meet the critical needs of our user group for such an instrument. This equipment will reside in our Proteomics Core Laboratory where resources available for administering use of the instrument include: 1) system management, maintenance, and cost recovery; and 3) skilled personnel with substantial experience with mass spectrometric methods. Availability of such instrumentation would allow our PHS-funded user group to pursue innovative research that currently is severely limited due to lack of such state-of-the-art instrumentation. II. Relevance: Our user group comprises elements of both basic and clinical research whose work is aimed at improving human health through discovery in such areas as HIV/AIDS, stroke, traumatic brain injury, cardiac arrest, mental health disorders, cancer, pulmonary hypertension, and transplantation. The acquisition of this hybrid triple quadrupole/linear ion trap mass spectrometer would provide essential instrumentation for this research and thereby remove impediments to research progress. [unreadable] [unreadable] [unreadable]